Loss of ZC3H12A Expression Is Linked to Higher Mortality Risk and Increased Lymphatic Metastasis in Oral Squamous...

Zinc finger CCCH-type containing 12A (ZC3H12A), also known as monocyte chemotactic protein-induced protein 1, has emerged as having a potential role in the landscape of some human cancer types, contributing to anti-tumorigenesis through signaling pathways of inflammation, apoptosis, autophagy and angiogenesis. However, its specific impact on the prognosis of oral squamous cell carcinoma (OSCC) remains to be investigated.

We conducted in-vitro cell models in a pilot study and performed a retrospective cohort study involving 242 patients with OSCC to unravel the association between ZC3H12A expression level and oral cancer prognosis during 3, 5, and 10-year follow-up.

The findings showed that endogenous ZC3H12A expression was decreased in both the malignant (BQO) and highly metastatic (HSC-3-M3) OSCC cell lines compared to dysplastic oral keratinocytes (DOK) and the parental cell line of HSC-3-M3 (HSC-3). The analysis of clinical cancerous tissue arrays from patients with OSCC showed a significant association between complete loss of ZC3H12A expression and heightened cancer mortality, particularly at 3 and 5 years. Moreover, the complete loss of ZC3H12A expression may be associated with increased risk of lymph node involvement in OSCC.

Our investigation suggests that the complete loss of ZC3H12A expression exacerbated the unfavorable prognosis of OSCC in this Taiwanese population, but further study on elucidating the gradual decline of ZC3H12A expression in OSCC is imperative.